The prospective of liquid crystals in nano formulations for drug delivery systems

By Rakesh K. Sindhu, Simona Cavalu et al.

https://doi.org/10.1016/j.molstruc.2021.131117

Liquid crystals (LCs) are also known as mesophase, which means an intermediate state between conventional solids and isotropic liquid, being mostly classified into two types: thermo tropic LCs (phase transition as a function of temperature) and lyotropic LCs (phase transition as a function of concentration of amphiphiles). Important features like thermodynamic stability, improved solubility of hydrophobic drugs, improved bioavailability and controlled release pattern made them effective carriers for a variety of drugs and bioactive compounds. Due to these unique features, LCs possess wide applications in the field of pharmaceuticals and become an attractive choice of vehicle for in vivo drug delivery. This review paper aims on highlighting the concept of LCs, classification, preparation methods and characterization techniques, in the context of pharmaceutical applications along with its perspectives in drug delivery systems. (Rajni Bala, Rakesh K. Sindhu, Bharti Kaundle, Reecha Madaan, Simona Cavalu, JOMS 1245, 2021, 131117)

Surface properties of collagen-functionalized aluminosilicate particles embedding iron and dysprosium designed for cancer therapy

By S. Simon, Simona Cavalu , D. Eniu, V. Simon

https://doi.org/10.1016/j.molstruc.2021.130341

Simultaneous radiotherapy and hyperthermia yield synergistic improvement of therapeutic efficacy in cancer therapy. The study is focussed on sol-gel derived particles of 60SiO2•20Al2O3•10Fe2O3•10Dy2O3 (mol%) system functionalized with type I collagen. The addition to aluminosilicate matrix of Fe2O3•was thought for hyperthermia and of Dy2O3 for internal radiation therapy after neutron activation of dysprosium to 165Dy radioisotope. The collagen functionalization of these particles aimed to make them well accepted in the body and to contribute to destruction of reactive oxygen species, what has to be taken into account when nanoparticles are used for cancer therapy.

The XRD, FTIR and XPS investigations were carried out on Fe-Dy-aluminosilicate particles of average size around tens of nanometers, before and after their incubation in collagen solution in order to prove the protein functionalization particles and to assess the changes in secondary structure of protein following this process. The results show the anchoring of the protein on particles surface in a few nanometers thin layer as well as some relative changes of protein secondary structure. After interface processes with particles surface, the secondary structure of amide I in collagen consists overwhelmingly of α-helices and only about 12 % of β-turns structure (S. Simon, Simona Cavalu, D. Eniu, V. Simon, JOMS 1236, 2021,130341).

Improved cytocompatibility and antibacterial properties of zinc-substituted brushite bone cement based on β-tricalcium phosphate

By Inna V. Fadeeva, Margarita A. Goldberg, Ilya I. Preobrazhensky, Georgy V. Mamin, Galina A. Davidova, Nadezhda V. Agafonova, Marco Fosca, Fabrizio Russo, Sergey M. Barinov, Simona Cavalu & Julietta V. Rau

Full text at https://link-springer-com.am.e-nformation.ro/article/10.1007%2Fs10856-021-06575-x

Brushite cements based on powders of Zinc (Zn) (1.4 wt%) substituted tricalcium phosphate (β-TCP) and non-substituted β-TCP were prepared and investigated by SEM/XRD, MTT test and microbiology assay. Copyright J. Rau, Simona Cavalu et al.

Zinc (Zn) is an important biological trace element that plays a role in the normal growth and development of the skeleton. Its content in human bones (0.0126–0.0217 wt%) is about 28% of the total amount of Zn in the body (0.0030 wt% of Zn in tissues) [20]. The lack of Zn slows down the growth of the bone mass and has a negative influence on the bone metabolism [21]. On the other hand, Zn deficiency is a factor of risk for bone osteoporosis [22]. 

XRD spectra of: TCP-based cement (A) before and (B) after soaking in physiological solution and Zn-substituted TCP cement (C) before and (D) after soaking in physiological solution. Copyright J. Rau, Simona Cavalu et al.
FTIR spectra of: A non-substituted and Zn-substituted TCP powders, B non-substituted and Zn-substituted TCP cements, and C non-substituted and Zn-substituted TCP cements after soaking in physiological solution. Copyright J. Rau, Simona Cavalu et al.
Comparison of EPR spectra for Zn-TCP powder sample annealed at 900 °C before and after X-ray irradiation. Copyright J. Rau, Simona Cavalu et al.
Bone Cements’ morphology, SEM images: AB cement based on β-TCP; CD cement based on Zn-β-TCP; EF cement based on β-TCP after soaking in physiological solution; GH cement based on Zn-β-TCP after soaking in physiological solution.
Copyright J. Rau, Simona Cavalu et al.
The inhibition of growth of: E. Coli for A Zn-TCP cement and B TCP cement; C E. faecium, and D P. aeruginosa for Zn-TCP cement (1) and TCP cement (2). The Zn-substituted TCP cement shows a stronger antibacterial activity, which is expressed in a larger bacterial zone of inhibition, with respect to the TCP cement. Copyright J. Rau, Simona Cavalu et al.

In this work, the cement based on the Zn-substituted β-TCP powder with a simplified preparation recipe and improved characteristics was developed. The setting time of cements was 8 min (the ratio of cement powder: hardening liquid = 3:1), which is optimal for preparation and application of the developed cements for bone defects during surgery. The Zn2+ content was selected to be 1.40 wt%. The pH of the cements reached 6.5 within 60 min after setting. After soaking in physiological solution for 60 days, the morphology and composition of cements changed. The final phases were DCPD and HA.The EPR measurements showed the presence of the trapped hydrogen and confirmed that annealing at 900 °C led to the significant reduction of carbonate impurities embedded into the β-TCP structure.The NCTC L929 fibroblast cell viability on the developed Zn-β-TCP cement was 10% higher compared to cement without Zn and possess antibacterial properties against E. coli, E. faecium, and P. aeruginosa.This finding confirms that the novel material could be a valid strategy for a range of biomedical application in humans. Therefore, it could offer promising potential for bone replacement and repair in moderate and non-load-bearing defects that are prone to infection in orthopedic and trauma setting.

Evaluation of In Vitro Wound-Healing Potential, Antioxidant Capacity, and Antimicrobial Activity of Stellaria media (L.) Vill

By F. M. Groza, S. I. Vicas, Simona Cavalu et al.

Stages of wound healing and the implications of fibroblasts in this process.
Copyright F. Groza, Simona Cavalu et al.

The main aim of our work was to highlight the in vitro healing potential of Stellaria media (L.) Vill. (SM) extract using the scratch assay on normal human dermal fibroblasts (NHDF). The ability to stimulate cell migration and proliferation under the influence of different concentrations of SM extract (range between 12.5 and 200 µg/mL) was determined compared to the control (untreated in vitro-simulated wound) and positive control (allantoin 50 µg/mL).Our findings demonstrate, for the first time in the literature, the wound-healing potential of SM extract on NHDF using the in vitro scratch method. 

Effect of Stellaria media extract concentrations (between 12.5 µg/mL and 200 µg/mL) on viability of NHDF after 24 h. Copyright F. Miere, Simona Cavalu et al.
The evolution over time (0, 12, 24, 36, and 48 h) of cell wound coverage at different concentrations of Stellaria media (L.) Vill extract (range 200 µg/mL–12.5 µg/mL) compared to positive control (CTRL)—treated with allantoin 50 µg/mL and untreated wound control (CTRL0). Fibroblasts marked in pink are those that have mobilized into the wound. The scale of the processed images is 100 µm. Copyright F. Groza, S. I. Vicas, Simona Cavalu et al.
The evolution of the cell density parameter inside the wound depending on the applied treatment and time. Copyright F. Groza, Simona Cavalu et al.
Evolution over time, of the average values of the widths (µm) of the wound, the areas (mm2) of the wound, of the normalized densities (%) of the cells inside the wound, and the Lp norm, for all treatments. C200—12.5 µg/mL represents the Stellaria media (L.) Vill extract concentrations applied, CTRL—positive control (allantoin—50 µg/mL), CTRL0—control (without treatment), where no treatment was applied. T00–T48 represents the time expressed in hours. Copyright F. Groza, Simona Cavalu et al.

Full text at https://www.mdpi.com/2076-3417/11/23/11526/htm

Nanoparticles and Nanostructured Surface Fabrication for Innovative Cranial and Maxillofacial Surgery

By Simona Cavalu et al.

Titanium cranioplasty procedure in the case of a large defect. Copyright Simona Cavalu et al.

The Importance of Nano-Structured Surface on Titanium Implants. Titanium mesh or plates can be used in cranioplasty either alone or in conjunction with other synthetic materials, such as hydroxyapatite, calcium phosphate, and polyethylene.

Light microscopy image in phase contrast, longitudinal section, 500×, Kroll reagent; (b) Scanning Electron Microscopy 2000×; (c,d) 3D and 2D Atomic Force Microscopy images; (e) contact angle investigation on the surface of the titanium mesh. Copyright Simona Cavalu et al.
Surface properties of Ti mesh for cranioplasty evidenced by different microscopic techniques. Copyright Simona Cavalu et al.
The main sequence of events occurring in vivo, during interaction between Ti surface and biological environment. Copyright Simona Cavalu et al.
(a) The flow chart of SeNPs production via hydrothermal reaction using different saccharides as reducing agent; (b) TEM image of SeNPs used for the surface modifications of Ti mesh for cranioplasty, along with the surface morphology of the coating upon in situ SeNPs deposition and details of fibroblasts adhesion on the nanostructured Ti surface.
Copyright Simona Cavalu et al.

This review emphasized the main reasons why titanium mesh is preferred for skull reconstructions along with the importance of developing innovative surface structures with a dual benefit in terms of improved osteointegration and enhanced antibacterial activity to reduce the risk of post-surgical infection, knowing that infections are the main complication in cranioplasty surgeries.

The full text of this paper

https://www.mdpi.com/1996-1944/13/23/5391/htm

Exploring Pharmacological Mechanisms of Essential Oils on the Central Nervous System

By

Giselle A. Borges e Soares, Tanima Bhattacharya, Tulika Chakrabarti, Priti Tagde and Simona Cavalu

https://www.mdpi.com/2223-7747/11/1/21

Biological effects of essential oils on the CNS through activation of various components of the brain. Copyright Simona Cavalu et al.

Since ancient times, essential oils (EOs) have been widely used and have been identified as therapeutic agents owing to their pharmacological and psychological properties. They were deemed to be physical, spiritual, and mental healing agents [1,2]. EOs are naturally occurring complex mixtures of volatile odor compounds synthesized as secondary metabolites by plants and are extracted through steam distillation, solvent extraction, maceration, cold press extraction, water distillation, and CO2 extraction. Novel methods that are more efficient and provide higher yields include supercritical fluid extraction, microwave-assisted extraction, and ultrasound [3]. Studies conducted on animals and humans have shown that EOs can produce a variety of CNS targeted pharmacological effects such as anxiolytic effect, neuroprotection, antidepressant effect, anticonvulsant effect, analgesic, and sedative effect, to name a few. As a result, EOs can be used as an adjuvant therapy to prevent and relieve symptoms associated with CNS-based disorders such as insomnia, depression, dementia, Alzheimer’s disease (AD), etc. As they are naturally occurring, they have the added benefit of being non-toxic and safe when utilized correctly at appropriate concentrations, which have been proven through research in the last ten years.

AuNPs as anticancer therapeutics. Copyright Simona Cavalu et al.
Role of essential oils in acetylcholine release and degradation. Copyright Simona Cavalu et al.

Potentiality of Nanoenzymes for Cancer Treatment and Other Diseases: Current Status and Future Challenges

By R. K. Sindhu, A. Najda, P. Kaur, M. Shah, H. Singh, P. Kaur, M. J. Sierocinska, Md. Habibur Rahman and Simona Cavalu

Copyright Simona Cavalu et al.
Nanozymes. Copyright Simona Cavalu et al.

Nanozymes can be controlled remotely via stimuli including heat, light, magnetic field, and ultrasound. Collectively, these all can be used to increase the therapeutic as well as diagnostic efficacy. 

Copyright Simona Cavalu et al.
Sources, properties, mimicking types, and analytical capabilities of nanozymes. Copyright Simona Cavalu et al.
Copyright Simona Cavalu at al.
Opportunities in the field of nanozymes. Copyright Simona Cavalu et al.
Copyright Simona Cavalu et al.
PtNPs/GO nanozymes for detecting cancer cells with calorimetric strategy.
Copyright Simona Cavalu et al.

The enzyme-mimicking properties of nanoparticles have proved to be significant in medicine, industry, and healthcare.

https://www.mdpi.com/1996-1944/14/20/5965/htm

Severe Cardiac and Metabolic Pathology Induced by Steroid Abuse in a Young Individual

By Adrian Tirla, Cosmin Mihai Vesa and Simona Cavalu

A case of a 25 year old patient with a complex medical history after 6 months of steroid administration. Myocardial infraction, dyslipidemia, obesity, hyperuricemia, secondary diabetes, and chronic renal disease were identified after clinical and para-clinical examinations. The particularities of this case were interpreted in the context of a literature review, highlighting the effect of multi-organ damage as a result of the uncontrolled use of anabolic steroid supplements.

https://www.mdpi.com/2075-4418/11/8/1313

Revisiting Therapeutic Strategies for H. pylori Treatment in the Context of Antibiotic Resistance: Focus on Alternative and Complementary Therapies

By I.A. Cardos, D. C. Zaha, R.K. Sindhu and Simona Cavalu

Copyright Simona Cavalu et al.
Carcinogenic effect of H. pylori through different mechanisms. Copyright Simona Cavalu et al.
Copyright Simona Cavalu et al.
H. pylori infections and alternative treatment approaches. Copyright Simona Cavalu et al.

H. pylori is responsible for a chronic, transmissible, infectious disease and the increasing prevalence of antibiotic resistance has complicated the therapy. All therapies should assume the possibility of antimicrobial drug resistance.

In the context of increasing rates of antibiotic-resistant H. pylori strains, the risk factors and prevalence on global population, the aim of our work is to highlight the main drawbacks of currently used treatment regimens against H. pylori and at the same time, to emphasize the huge potential of natural alternatives, plants extracts and new formulation design and strategies to combat this pathogen. Special attention is also given to nanotechnological formulations, with huge potential for tissue microenvironment-responsive treatment. Copyright Simona Cavalu et al.

Nanotechnology-Based Approach against H. pylori Infections

Metallic NPs such as silver, gold, zinc or iron have been previously reported to possess the ability of killing a wide range of bacteria including H. pylori [153,154] by well-known underlying mechanisms involving oxidative stress, metal ion release and nonoxidative stress. A very low NPs concentration is necessary for bactericidal effect, and hence, it is difficult for the bacteria to develop resistance. Among different metallic NPs, AgNPs are convenient, especially the biologically derived ones, as the preparation methods demonstrated a controlled particle size, shape, and mono-dispersity, while reducing time of preparation, in the context of environmentally friendly approaches. Copyright Simona Cavalu et al.

https://www.mdpi.com/1420-3049/26/19/6078

The power of plants. Evaluation of Wound Healing Potential of Novel Hydrogel Based on Ocimum basilicum and Trifolium pratense Extracts

By Simona Cavalu et al.

Copyright Simona Cavalu et al.
Hydrogel original formulation. Copyright Simona Cavalu et al.

The preparation of gel formulation containing Trifolium pratense L. and Ocimum basilicum L. extract.

Copyright Simona Cavalu et al.
Spontaneous migration of dermal fibroblasts and evolution of “gap’’ closure in time: Copyright Simona Cavalu et al.
Copyright Simona Cavalu et al.
Evolution of the migration of fibroblasts and “gap coverage” (which is similar to wound closure), with respect to the statistical factor “Sample”. Copyright Simona Cavalu et al.
Copyright Simona Cavalu et al.
Animal model. Evolution in time (contraction) of the wound healing process in both groups (the control group and the EOT hydrogel-treated group). Copyright Simona Cavalu et al.
Copyright Simona Cavalu et al.
Clinical aspects of Psoriasis vulgaris treated with gel formulation of Ocimum basilicum and
Trifolium pratense extract mixture. Copyright Simona Cavalu et al.

https://www.mdpi.com/2227-9717/9/11/2096

Electrochemical (Bio)Sensors with improved performances for Biomedical Applications

By L. Fritea, Simona Cavalu et al.

Metal Nanoparticles and Carbon-Based Nanomaterials for Improved Performances of Electrochemical (Bio)Sensors with Biomedical Applications

 A “real-time” biosensor includes a biological recognition receptor (such as an antibody, enzyme, nucleic acid or whole cell) and a transducer to convert the biological binding event to a detectable signal, which is read out indicating both the presence and concentration of the analyte molecule.In nano(bio)sensors, nanoparticles (NPs) are incorporated into the (bio)sensor design by attachment to the suitably modified platforms. For this purpose, metal nanoparticles have many advantageous properties making them useful in the transducer component of the (bio)sensors. Gold, silver and platinum NPs have been the most popular ones, each form of these metallic NPs exhibiting special surface and interface features, which significantly improve the biocompatibility and transduction of the (bio)sensor compared to the same process in the absence of these NPs. The main types of NPs used for electrochemical (bio)sensors design, especially screen-printed electrodes, with their specific medical application due to their improved analytical performances and miniaturized form is presented.

Copyright Simona Cavalu et al.
Schematic representation of main synthesis methods of metal NPs and carbon-based nanomaterials. Copyright Simona Cavalu et al.
Copyright Simona Cavalu et al.
Some examples of commercially available screen-printed electrodes (from different manufacturers: Copyright Simona Cavalu et al.

This comprehensive review is focused on the main types of metal NPs and carbon-based nanomaterials used for electrochemical (bio)sensors design, especially screen-printed electrodes, with their specific biomedical applications, improved analytical performances and miniaturized form.Nanotechnological approaches will extend the limits of currently employed (bio)sensors and, moreover, they will open a new window toward personalized medicine, offering new solutions to the main challenges in the diagnostic and therapeutic fields. Future research should focus on some improvements concerning the nanomaterials characteristics and the sensor design in order to enhance their performances with multi-disciplinary efforts. The real sample analysis with more enhanced sensitivity and selectivity is still a challenge for researchers aiming the validation of the electrochemical nano(bio)sensors in comparison with the traditional analytical procedures. The reproducibility is another key aspect which needs to be solved for large-scale production of electrochemical sensors and their introduction on commercial market. The miniaturized, portable or wearable sensors which can perform on-site and real-time analysis will gain tremendous importance at the commercial level, with a huge impact on the health system.

The full text of this paper is available at

https://www.mdpi.com/1996-1944/14/21/6319/htm

Liposomes for oral delivery of Berberine

By H.I. Kutbi, H.Z. Asfour, A. K. Kammoun, A. Sirwi, H. A. Gad and Simona Cavalu

Optimization of Hyaluronate-Based Liposomes to Augment the Oral Delivery and the Bioavailability of Berberine

To improve Brb permeability and bioavailability, this study presents a newly developed formulation, namely Brb hyaluronate-based liposomes, prepared by using film hydration method and characterized by dynamic light scattering measurements, entrapment efficiency percentage (EE%), transmission electron microscope (TEM), in vitro drug release and physical stability. Results of pharmacokinetics studies indicated the potential of the liposomal formulation to increase the oral bioavailability of Brb and to accelerate its entry into the bloodstream. The obtained results are accredited to the lipophilic nature of the prepared system, resembling the structural features of bio-membrane, in addition to their small size that enhances intestinal penetration. 

Berberine hyaluronate based liposomes. Copyright H. A. Gad and Simona Cavalu
Transmission electron microscope of berberine hyaluronate based liposomes, showing the nearly spherical shape (A) and the multi-lamellar structure of the vesicles bilayer (B) of the prepared liposomes. Copyright H. A. Gad and Simona Cavalu
The effect of the independent variables on liposomes particle size and entrapment efficiency percent. Copyright H. A. Gad and Simona Cavalu
Three-dimensional (3D) response surface plots showing the effect of the independent variables on liposomes particle size and entrapment efficiency percent: A—total lipid amount (mg), B—berberine (mg), C—hyaluronic acid (mg). Copyright H. A. Gad and Simona Cavalu
Plasma concentration profiles of berberine in rats after oral administrations. Copyright H.A. Gad and Simona Cavalu
Plasma concentration profiles of berberine in rats after oral administrations of 50 mg/kg of berberine in various formulations. Each point represents mean ± standard deviation (N = 6). Copyright H.A. Gad and Simona Cavalu

Different formulation variables (lipid, drug and hyaluronic acid amounts) have a significant effect on the physicochemical characteristics of the prepared system using film hydration method. The presence of hyaluronic acid as a main component in liposomes preparation was able to slow berberine diffusion from the vesicles.Oral administration of Brb hyaluronate-based liposomes to rats could improve lipophilicity and bioavailability of the investigated system compared to Brb solution and Brb liposomes prepared without hyaluronic acid. Copyright H.A. Gad and Simona Cavalu

The full text of this paper is available at

https://www.mdpi.com/1996-1944/14/19/5759/htm

Carbon Nanotubes for Improved Performances of Endodontic Sealer

By Simona Cavalu et al.

In order to overcome the limitations of current endodontic sealers, especially against resistant bacteria, recent developments in the field of nanotechnology have proved the necessity to reconsider the composition and physico-chemical properties of classical sealers. Nanoparticles with their unique features in terms of small size and high specific surface area, are the best choice for incorporation of antiseptic agents and effective delivery. Multi-walled carbon nanotubes (MWCNTs) encapsulating chlorhexidine (CHX) and colloidal silver nanoparticles (AgNPs) were prepared and incorporated into commercial sealer and investigated in terms of bonding performance to dentin and effectiveness against E. faecalisS. aureus and Candida albicans, which are responsible for the majority of the failures in endodontic treatments. In this context, the challenges related to the long-term biological effects of CHX/AgNPs loaded MWCNTs are discussed.

Development of “smart” endodontic therapeutic agents 

SEM morphological details of CNTs. Copyright Simona Cavalu
SEM morphological details of CNTs as received from the manufacturer, before (a) and after (b) loading with the mixture CHX/AgNPs (High magnification, 100,000×).
Copyright Simona Cavalu et al.
Colloidal CNTs in distilled water (left) compared to colloidal mixture CHX/AgNPs. Copyright Simona Cavalu
SEM morphological details of CNTs as received from the manufacturer, before (a) and after (b) loading with the mixture CHX/AgNPs (High magnification, 100,000×); (c) photographic image of colloidal CNTs in distilled water (left) compared to colloidal mixture CHX/AgNPs (right). Copyright Simona Cavalu et al.
SEM  details of commercial  and modified root canal sealer. Copyright Simona Cavalu
Ultrastructure details of commercial (a) and modified root canal sealer (c) along with the corresponding EDX spectrum (b,d). Copyright Simona Cavalu et al.
Load–displacement curves and Young modulus calculation. Copyright Simona Cavalu.
Load–displacement curves (a) recorded on the surface of commercial (black) and modified sealer (red) and the corresponding Young modulus calculation (b). Copyright Simona Cavalu et al.
TGA and DTG thermograms of the modified and commercial sealers.
Copyright Simona Cavalu et al.
SEM images of interfacial adaptation between sealer and root canal dentine. Copyright Simona Cavalu
SEM images of interfacial adaptation between sealer and root canal dentine. Copyright Simona Cavalu
SEM images (a,c) of interfacial adaptation between sealer and root canal dentine (polished specimens) along with the corresponding EDX spectra (b,d): (a) neat sealer;
(c) CNTs/CHX/AgNPs modified sealer. The transversal section was performed in the middle zone of the root. Copyright Simona Cavalu et al.
Antimicrobial and antifungal effect of different combinations and the mixture CNTs/AgNPs/CHX2%
Antimicrobial and antifungal effect of different combinations and the mixture CNTs/AgNPs/CHX2% against the tested strains. Data are expressed as average value ± standard deviation of triplicate samples (statistical significance * p < 0.05).
Copyright Simona Cavalu

Our original approach, in the context of new generation sealers expecting to have a long-lasting antimicrobial effect, was to demonstrate that the antimicrobial effect of the mixture CNTs/AgNPs/CXH 2% incorporated in commercial sealer, was preserved long enough to efficiently inhibit Gram-positive germs, with excellent results towards E. faecalis in a concentration of 1 mg/mL. The antibacterial and antifungal assay clearly demonstrated a synergic effect of AgNPs, CHX 2% and CNTs with excellent results towards E. faecalis, which is responsible for the primary etiologic factors in pulp and periapical lesions.

The full text of this paper is available at

https://www.mdpi.com/1996-1944/14/15/4248/htm